P699: REAL-LIFE OUTCOMES OF PONATINIB TREATMENT IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA (CML) OR PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ALL): 5-YEAR-DATA FROM A BELGIAN REGISTRY
Authors: T. Devos, V. Havelange, K. Theunissen, S. Meers, F. S. Benghiat, A. Gadisseur, G. Vanstraelen, H. Vellemans, B. Bailly, N. Granacher, P. Lewalle, A. De Becker, K. Van Eygen, M. Lejeune, M. Janssen, A. Triffet, I. Vrelust, D. Deeren, D. Mazure, M. Beck, H. Sebti, D. Selleslag
Journal: HemaSphere (2022)

Background: Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for adult patients with chronic, accelerated or blast phase CML resistant or intolerant to nilotinib or dasatinib or with Ph+ALL resistant or intolerant to dasatinib or for patients with the T315I mutation. Real-world data on ponatinib treatment are limited but are important to evaluate the effectiveness and safety of ponatinib and optimize its use in daily practice. Aims: To report 5-year-Belgian registry data on ponatinib use in CML and Ph+ALL patients in routine clinical practice. Methods: This ongoing prospective multi-center registry (NCT03678454) includes ≥18-year-old patients with CML or Ph+ALL eligible for ponatinib treatment per product label. Data on demographics, effectiveness (major molecular response [MMR] rate) and safety were collected for patients enrolled from 01-March-2016 onwards and are presented here up to 17-May-2021. Results: In this interim analysis, 77 patients from 21 hospitals were enrolled (50 CML, 27 Ph+ALL). Of the 28 patients (39%; 14 CML, 14 Ph+ALL) with mutations in the BCR-ABL1 kinase domain, 17 (8 CML, 9 Ph+ALL) had the T315I mutation at entry. Median age at ponatinib start was 61 years for CML and 56 years for Ph+ALL patients. 88% of CML and 96% of Ph+ALL patients had received ≥2 prior TKIs. Potential pre-existing risk factors for TKI cardiovascular toxicity were observed: history of cardiovascular disease (27 patients), hypertension (23), smoking (15), diabetes (13), hypercholesterolemia (8), hyperlipidemia (6). The most frequently reported risk factor was history of cardiovascular disease (36% CML, 33% Ph+ALL). Median follow-up was 545 (14-3190) days for CML and 210 (26-2933) days for Ph+ALL patients. Reasons for starting ponatinib therapy were intolerance to previous TKIs (26 CML, 11 Ph+ALL), relapse on/refractoriness to previous TKIs (11 CML, 8 Ph+ALL), T315I mutation (6 CML, 6 Ph+ALL) and disease progression (7 CML, 2 Ph+ALL). Ponatinib starting doses were: 45 mg/day (66%), 30 mg/day (10%), 15 mg/day (22%) in CML patients (1 patient started with 15 mg every 2 days) and 45 mg/day (67%), 30 mg/day (15%), 15 mg/day (19%) in Ph+ALL patients. MMR was achieved in 58% of CML and 52% of Ph+ALL patients. The median time-to-MMR was 170 days in CML and 86 days in Ph+ALL patients. Of the 37 patients who started ponatinib due to intolerance to previous TKIs, 59% (15 CML, 7 Ph+ALL) achieved MMR. Adverse reactions (ARs) were reported in 63 patients (82%); the most common were rash (23% of all), constipation (18% of CML) and headache (11% of Ph+ALL patients). Seventeen patients developed 26 serious AR. Serious cardiovascular ARs were reported in 7 patients (coeliac artery stenosis [in 2 patients], ischemic stroke [1], worsening hypertension [1], hypertension [1], deep venous thrombosis [1], possible transient ischemic attack [1]). Eight deaths were recorded, none related to ponatinib treatment. 56% of CML and 24% of Ph+ALL patients discontinued ponatinib treatment due to an AR. Summary/Conclusion: This real-world Belgian registry over 5 years supports the use of ponatinib in CML and Ph+ALL patients resistant or intolerant to previous TKIs or carrying the T315I mutation. Results obtained in routine clinical practice are in concordance with clinical trials, including PACE, in which CML patients had durable and clinically meaningful responses to ponatinib. Funding: Incyte Biosciences Benelux BV Acknowledgements: Medical writing support was provided by Adina Truta (Modis)